LIFR (LIF receptor subunit alpha) is a cytokine receptor that functions as a signal-transducing molecule in the JAK/STAT3 pathway 1. It acts as a coreceptor that binds leukemia inhibitory factor (LIF) and oncostatin M (OSM) in complex with GP130, triggering downstream signaling cascades including MAPK, AKT, and mTOR activation 2. LIFR regulates cell proliferation, differentiation, and immune cell modulation within tumor microenvironments 3. In cancer, LIFR exhibits context-dependent roles. In solid tumors and glioblastoma, LIF/LIFR overexpression drives tumor growth, progression, metastasis, and therapy resistance through JAK/STAT3 activation, promoting cancer stemness via SOX2 transcription 42. Conversely, LIFR downregulation in hepatocellular carcinoma and breast cancer appears oncogenic, promoting tumorigenesis through NF-κB pathway activation and ferroptosis resistance 56. LIFR promoter methylation frequently silences LIFR expression in breast cancer, correlating with poor prognosis 6. Clinically, LIFR mutations cause Stüve-Wiedemann syndrome, an autosomal recessive bent-bone dysplasia with respiratory complications 1. Therapeutic approaches include targeting LIF/LIFR signaling with monoclonal antibodies and receptor inhibitors in cancer, with clinical trials ongoing 2.